This invention relates to the use of polymer additives to peritoneal dialysis solutions, principally for use in the medical procedures of intermittent peritoneal dialysis (IPD) and continuous ambulatory peritoneal dialysis (CAPD).
Currently, the most widely used method of kidney dialysis for treatment of End Stage Renal Disease (ESRD) is "hemodialysis". Here, the patient's blood is cleansed by passing it through an artificial kidney in an artificial kidney dialysis machine. By the process of diffusion across a semipermeable membrane in the artificial kidney into a dialysis solution, impurities and toxins are removed from the patient's blood to thereby perform a natural function of the patient's kidneys. Water is also removed from the patient's blood, the water diffusing across the membrane of the artificial kidney into the dialysis solution; this process is called ultrafiltration.
Hemodialysis is generally required three times a week, each dialysis requiring 4 to 5 hours in a dialysis center or at home. During dialysis, the patient is "tied" to the machine by venous and arterial blood lines which convey his blood to and from the artificial kidney.
Although used less frequently than hemodialysis, a procedure known as "intermittent peritoneal dialysis" (IPD) is an accepted method for treating ESRD. In this procedure, a dialysis solution, typically containing dextrose as an osmotic agent, is infused into the patient's peritoneal cavity by means of tubing and a catheter. The peritoneum, which defines the peritoneal cavity, contains many small blood vessels and capillary beds which act as a natural semipermeable membrane. This natural membrane may be contrasted with the artificial membrane used in hemodialysis. In both cases, however, impurities, toxins, and water in the blood are removed by diffusion across a membrane--a cellulose membrane of an artificial kidney or a peritoneal membrane of a peritoneal cavity.
In intermittent peritoneal dialysis, dialysis solution remains in the patient's peritoneal cavity for a time sufficient for blood impurities and water to be removed by diffusion across the peritoneal membrane and into the dialysis solution. The impurity and water containing dialysis solution then is drained from the peritoneal cavity by means of a catheter and tubing, and a fresh supply of dialysis solution is infused. Intermittent peritoneal dialysis utilizes pumps or other auxillary equipment to which the patient is "tied" during dialysis; here also the patient must remain sedentary.
"Continuous ambulatory peritoneal dialysis" (CAPD) is another type of peritoneal dialysis which uses the peritoneum as a semipermeable membrane. The continuous procedure has the important advantage, however, of enabling the patient to be ambulatory and conduct a normal routine during dialysis. The patient is not "tied" to a machine, and he must be sedentary only for the time required to drain and infuse dialysis solution from and into the peritoneal cavity. This infusion and draining is handled by tubing and a surgically implanted, indwelling catheter in the patient's abdominal wall and in communication with his peritoneal cavity.
In a preferred method of practicing this procedure, the patient fills his peritoneal cavity with dialysis solution, typically the same dextrose-containing dialysis solution used in IPD, from a collapsible plastic container. When the container is empty, it is not disconnected from the tubing leading into the patient's peritoneal cavity. Instead, the patient simply rolls up or folds the container and tucks it into his clothing. When it is time to drain the solution from his peritoneal cavity he removes the folded container and drains directly into it. Once full, the patient then replaces the container with a container of fresh dialysis solution.
The currently used peritoneal dialysis solutions for IPD and CAPD which use dextrose as the osmotic agent have several disadvantages. A first disadvantage is that high dextrose concentration in the peritoneal dialysis solution causes dextrose to migrate through the peritoneum into the bloodstream, providing unwanted dextrose calories and possibly elevated triglyceride levels to the patient, and at the same time, reducing the osmolarity of the peritoneal dialysis solution. Unwanted dextrose is a particularly IPD or CAPD.
A second disadvantage is that dextrose in peritoneal dialysis solutions may cause the unwanted loss of amino acids and polypeptides from the blood of the patient.
Third, the pH of the dextrose-containing peritoneal dialysis solution (typically in the pH range 5.2-5.5) is not as physiologic as some physicians may desire.
It is therefore an object of the present invention to provide a peritoneal dialysis solution containing a primary osmotic agent other than dextrose that will not provide the unwanted calories and elevated triglycerides of dextrose to the patient.
It is another object of the invention to provide an osmotic agent which prevents the unwanted loss of amino acids and polypeptides from the blood of the patient.
It is a further object of the invention to provide a peritoneal dialysis solution which is in a more physiologic pH range than peritoneal dialysis solutions which use dextrose as the osmotic agent.
In accordance with this invention, polymer osmolarity-increasing agents are provided to peritoneal dialysis solutions, so that solutions of increased osmolarity and improved characteristics may be provided in which the patient does not receive unwanted dextrose into his bloodstream.
Furthermore, in accordance with this invention, peritoneal dialysis solutions may be provided in a more physiologic pH range than when dextrose is used as the osmotic agent and in which the loss of amino acids and polypeptides from the bloodstream is reduced.
Some of the preferred polymer additives to the peritoneal dialysis solutions are physiological materials related to foods, and appear to have essentially no toxicity, while at the same time providing a strong osmotic agent for the peritoneal dialysis solutions of this invention.
There is some published literature on polymer additives to peritoneal dialysis solutions. In the article by Rubin, Nolph, et al., entitled Osmotic Ultrafiltration with Dextran Sodium Sulfate Potential for Use in Peritoneal Dialysis from Journal of Dialysis, 3(263), 251-264 (1979), dextran sodium sulfate of a molecular weight of about 500,000 was evaluated in-vitro as a potential nonabsorbable osmotic agent for peritoneal dialysis. It was compared to poly (sodium acrylate) which had been shown previously to be effective in rats, but may have toxic characteristics; see Polymer Induced Ultrafiltration In Dialysis: High Osmotic Pressure Due To Impermeant Polymer Sodium, Nolph, et al., Vol. XXIV Trans. Am. Soc. Artif. Intern. Organs, pp 162-168 (1978).
Dextran sodium sulfate and poly (sodium acrylate), being of high molecular weight, can reside in the peritoneal cavity of a patient without diffusing through the peritoneum into the blood stream in significant quantities. Thus, the concept of the cited articles is to use these materials, with their multiple sodium ions associated with each molecule, to increase the osmolarity of the solution for the purpose of increasing the ultrafiltration or diffusion of water through the peritoneum from the blood to the dialysis solution.